The invention relates generally to solid supports for solid phase chemical synthesis.
The use of a variety of solid supports has been described for use in the synthesis of oligonucleotides.
Currently, controlled porosity glass (CPG) particles are used in large-scale oligonucleotide synthesis. However, these particles have limited capacities for loading and length of the nucleoside. More particularly, chemical loading levels for glass are limited to “native” silanol concentrations on the surface of the glass. For glass, there is a fixed quantity of silanol groups per unit surface area. The surface area is inversely proportional to the pore size. Thus, even though high pore sizes are favorable from a synthesis point of view, such CPG's have a low loading capacity compared to a polymeric support.
Thus, polymeric supports have been used for oligonucleoside synthesis, including, e.g., polystyrene-based particles. The use of low crosslinked polystyrene particles has been described for polypeptide synthesis. These do not accommodate high-yield oligonucleotide synthesis, due to their high degree of swelling in the synthesis solvents. Highly crosslinked particles have been used for large scale synthesis. Although this type of solid support swells much less, it has a limited nucleoside loading capability and is compressible.
In order to address these problems, polystyrene of intermediate crosslinking has been used to achieve higher loading capacities. These supports do swell considerably, and therefore, overall volumetric yield is compromised. Furthermore, compressibility is greater than that of the higher crosslinked polystyrene.
What are needed are additional solid supports for solid phase synthesis.